21 U.S.C. § 355a — Pediatric studies of drugs

(a) Definitions. In this section, "pediatric studies" (or "studies") means at least one clinical investigation of a drug in pediatric age groups — including newborns when appropriate — for a use the drug is expected to have. The Secretary can decide this includes pharmacokinetic studies (how the body processes the drug) and, at the Secretary's discretion, preclinical studies too. (b) Market exclusivity for new drugs. (1) In general. Before the Secretary approves a new drug application under section 355(b)(1), if the Secretary decides that pediatric information about the drug could produce health benefits for children, the Secretary can send the drug maker a written request for pediatric studies, including a deadline. If the maker agrees, completes the studies using the right formulations for each age group by the deadline, and the study reports are submitted and accepted under subsection (d)(4), then (unless paragraph (2)'s exception applies): (A) certain market exclusivity periods for the drug get longer — the 5-year period in section 355(c)(3)(E)(ii) and (j)(5)(F)(ii) becomes 5 years 6 months (with related 4-year, 48-month, and 7.5-year periods becoming 4.5 years, 54 months, and 8 years), or, alternatively, a 3-year period in certain clauses becomes 3 years 6 months; and if the drug is designated for a rare disease under section 360bb, its 7-year exclusivity under section 360cc(a) becomes 7 years 6 months; and (B) if the drug is covered by a listed patent with a certification submitted under specific paragraphs of section 355, and pediatric studies were submitted before the patent (and any extensions) expired, or if the drug is subject to a different type of certification, then the period during which a competing application cannot be approved gets extended by six months after the patent expires. The same six-month extension applies if the drug's patent certification led to infringement litigation and a court found the patent valid and infringed. (2) Exception. The Secretary will not grant this extension if the acceptance decision under subsection (d)(4) happens less than 9 months before the original exclusivity period would have expired. (c) Market exclusivity for already-marketed drugs. This works almost the same way as (b), but for drugs already on the market. If the Secretary decides pediatric information about an approved drug could produce health benefits for children, and sends a written request (with a deadline) to the holder of the approved application, and the holder agrees, completes the studies on time, and the reports are accepted under subsection (d)(4), then the same exclusivity extensions described in (b)(1)(A) and (B) apply. The same 9-month exception in (b)(2) applies too. (d) Conduct of pediatric studies. (1) Request for studies. After consulting with the drug's sponsor or holder, the Secretary can send a written request for pediatric studies. The request must account for adequate representation of children of ethnic and racial minorities. It must be in writing, include a timeframe, and ask the sponsor to propose pediatric labeling based on the results. If the request skips studies in newborns, it must explain why. A single written request may cover more than one use of the drug, including both approved and unapproved uses. (2) Written request for pediatric studies. Within 180 days of getting the written request, the sponsor or holder must tell the Secretary whether they will do the studies — either giving a start date, or explaining why they are declining. If they decline because a suitable pediatric formulation is not possible, they must explain why. If the sponsor or holder agrees to do the studies, they must give the Secretary all postmarket adverse event reports about the drug that they have, at the same time they submit the study reports. (3) Action on submissions. The Secretary must review and act on any proposed study request or amendment within 120 days of getting it. (4) Meeting the studies requirement. Within 180 days of getting the study reports, the Secretary must accept or reject them and notify the sponsor or holder. The Secretary can only judge whether the studies actually answer the written request, followed accepted scientific methods, and were reported the way the Secretary requires. (5) Effect of subsection. This subsection does not change section 331(j) of this title, section 552 of title 5, or section 1905 of title 18 (rules about trade secrets and confidential information). (6) Consultation. For a drug that qualifies as a countermeasure against a public health threat (as defined in specific sections of title 42), the Secretary must ask the Assistant Secretary for Preparedness and Response whether pediatric studies are needed, and ask the Director of the Biomedical Advanced Research and Development Authority how to conduct them. (e) Notice of determinations on studies requirement. (1) In general. The Secretary must publish notice whenever a drug meets subsection (d)'s requirements and becomes subject to this section for approvals under section 355(b)(2) or (j). This notice must come out within 30 days of the Secretary's exclusivity decision and must include a copy of the written request. (2) Identification of certain drugs. If a pediatric formulation was developed, studied, and found safe and effective, but is not put on the market within one year after the Secretary's notice under paragraph (1), the Secretary must publish a notice identifying that drug, within 30 days after that one-year period ends. (f) Internal review of written requests and pediatric studies. The Secretary must use the internal review committee (created under section 355d) to review all written requests before they are issued, and the committee may review completed studies and recommend to the Secretary whether to accept or reject them. The committee can act using just some of its members. For each drug, it must record which members took part in each review. The Secretary, working with the committee, must track and publicly post — including on the FDA website — things like: how many studies were done; which drugs and uses were studied; the types of studies (design, number of patients, number of study sites and countries); how many pediatric formulations were and were not developed, and why; labeling changes that resulted; an annual summary of those labeling changes; and information about reports submitted on or after September 27, 2007. The Secretary must also share with the committee any response given to a sponsor or holder about a proposed pediatric study request. (g) Limitations. Even though subsection (c)(2) sets a 9-month cutoff, a drug that has already gotten one six-month exclusivity extension under (b) or (c) can get another six-month period under (c)(1)(A)(i)(II) for a supplemental application, if it meets all other requirements — but not another one under (c)(1)(B), and not another one under (c)(1)(A)(ii) either. (h) Relationship to pediatric research requirements. Exclusivity under this section is only granted for finishing studies that were the subject of a written request, whose reports are submitted and accepted under (d)(4). A written request can be built around a study required under section 355c. (i) Labeling changes. Any application proposing a labeling change from a pediatric study under this section is automatically treated as a priority application, and must meet the Commissioner's timing goals for priority drugs. If, within 180 days of the application, the Commissioner and the sponsor cannot agree on labeling changes, the Commissioner asks the sponsor to make the changes; if the sponsor refuses within 30 days, the Commissioner sends the dispute to the Pediatric Advisory Committee, which must review the study reports and recommend labeling changes within 90 days. The Commissioner considers that recommendation and, within 30 days, may again ask the sponsor to make the changes. If the sponsor still refuses within 30 days, the Commissioner can treat the drug as misbranded. None of this limits the government's power to bring a separate enforcement action for missing pediatric labeling — using the Committee process does not block or delay an enforcement action, and vice versa. (j) Other labeling changes. If the Secretary decides that a pediatric study shows a drug is, is not, or inconclusively is safe and effective for children, the Secretary must order the drug's label to describe the study results and the Secretary's conclusion. (k) Dissemination of pediatric information. Within 210 days of a study report being submitted, the Secretary must make the medical, statistical, and clinical pharmacology reviews of that study public. The Secretary must require, as part of the written request, that sponsors whose studies led to labeling changes send that information to physicians and other health care providers at least once a year, or more often if needed for public health. This does not change the trade-secret and confidentiality rules in section 331(j), section 552 of title 5, or section 1905 of title 18. (l) Adverse event reporting. For the 18 months after a labeling change under subsection (i), the Secretary must send every adverse event report about that drug — no matter when it was received — to the Office of Pediatric Therapeutics. That Office's Director must have the Pediatric Advisory Committee review the reports, including recommending whether the Secretary should act. After that 18 months, the Secretary must still refer pediatric adverse event reports about the drug to the Office as appropriate, and the Director may still send them to the Committee. The Office can still send reports to the Committee even before the 18-month period starts, if needed to keep pediatric use of the drug safe. These review requirements add to, but do not replace, the Secretary's other review of adverse event reports. (m) Clarification of interaction of market exclusivity under this section and market exclusivity awarded to an applicant for approval of a drug under section 355(j). Sometimes a generic drug maker's 180-day exclusivity period under section 355(j)(5)(B)(iv) overlaps with a 6-month pediatric exclusivity period under this section, so the generic maker loses part of their 180 days. When that happens, the 180-day period gets extended by the number of overlapping days: starting from when the 180 days would have ended, if it would have ended after the 6-month period; or starting from when the 6-month period ends, if the 180 days would have ended during the 6-month period. (n) Referral if pediatric studies not submitted. If pediatric studies are not submitted by the deadline in the written request, or the sponsor or holder refuses the request, and the Secretary (through the section 355d committee) decides there is still a real need for pediatric information about the drug, the Secretary must: for a drug still under an unexpired listed patent, or unexpired exclusivity that could be extended under (b)(1), (c)(1), or related provisions of section 262 of title 42, decide whether to require an assessment under section 355c(b); for a drug with no unexpired patents or extendable exclusivity, refer it for inclusion on the study list under section 284m of title 42; and for a drug that is a qualified countermeasure, security countermeasure, or pandemic or epidemic product (as defined in specific sections of title 42), also notify the Assistant Secretary for Preparedness and Response and the Director of the Biomedical Advanced Research and Development Authority about all the pediatric studies in the written request. The Secretary must publicly explain any decision not to require an assessment. None of this changes section 331(j), section 552 of title 5, or section 1905 of title 18. (o) Prompt approval of drugs when pediatric information is added to labeling. A drug application under section 355(b)(2) or (j) cannot be denied approval, or called misbranded, just because its label leaves out a pediatric use or other pediatric information that is protected by a patent or by exclusivity (under specific provisions of section 355, section 360cc(a), or extensions of that exclusivity under this section or section 355f). Despite those same exclusivity provisions, the Secretary can still require the drug's label to say that, because of another manufacturer's marketing exclusivity, the drug is not labeled for a pediatric use, plus any pediatric warnings, precautions, or contraindications the Secretary thinks are needed for safety. Nothing in this subsection changes: the availability of exclusivity under this section, under section 355 for pediatric formulations, or under section 360cc; any extension of that exclusivity, including under this section or section 355f; whether an application that omits some other protected pediatric labeling is still eligible for approval; or, except as this subsection specifically says, how section 355 or section 360cc otherwise works.